Zingel V, Elz S, Schunack W
Institut für Pharmazie, Freien Universität Berlin.
Pharmazie. 1992 Oct;47(10):746-51.
Piperidinoalkyl-, morpholinoalkyl- or [(pyrid-2-yl)methylthio]alkyl-substituents were introduced into position 2 of the essential histamine structure. These 2-substituted histamine derivatives were prepared via reaction of imidate hydrochlorides in liquid ammonia under pressure with 1,3-dihydroxypropanone followed by a stepwise build-up of the side chain in position 4 of the imidazole nucleus (route I) or by cyclization with 2-oxo-4-phthalimido-1-butyl acetate (route II) followed by deprotection of the primary amine function. The novel compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-activity on the isolated guinea-pig right atrium. While 10a, c-e proved to be weak partial H1-agonists, 10b, f were very weak H1-antagonists.
将哌啶基烷基、吗啉代烷基或[(吡啶-2-基)甲硫基]烷基取代基引入到必需的组胺结构的2位。这些2-取代的组胺衍生物是通过在压力下于液氨中使亚氨酸盐酸盐与1,3-二羟基丙酮反应，然后在咪唑核的4位逐步构建侧链（路线I），或者通过与2-氧代-4-邻苯二甲酰亚胺基-1-丁酯环化（路线II），随后对伯胺官能团进行脱保护来制备的。对这些新化合物进行了分离豚鼠回肠上的H1活性和分离豚鼠右心房上的H2活性筛选。结果表明，10a、c - e是弱的部分H1激动剂，而10b、f是非常弱的H1拮抗剂。
